This invention provides a novel catalyst and method for the formation of amide bonds. The catalysts are derivatives of hydroxybenzotriazole (HOBT) and carry a positive charge at pH 5-7. These reagents are useful for forming compounds containing an amide bond with high purity and yield.
A wealth of procedures are available for forming amide bonds. Nonetheless, there is still room for improvement. For example, procedures have been developed which use reagents such as carbodiimides as amide coupling agents. These carbodiimides include dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC). Unfortunately, these particular reagents can require a large excess of acid, can be problematic for difficult couplings with unreactive carboxylic acids and/or amines and can be difficult to purify from the reaction mixture.
Catalysts such as 1-hydroxybenzotriazole (HOBT) and derivatives thereof have also been used. ##STR2##
Unfortunately, HOBT and its derivatives can be difficult to remove from the reaction media.